and vegan dairy alternatives. Currently, the growth of vegan yeast extracts, stevia, vitamins and other food supplements. alternatives to cows’ milk is a strong market driver. Preferring The combination of its vast application know-how and its Using in vivo models to support development of drinks made from soy, oat, spelt or almonds, many consumers huge armory of ingredients enables the company to develop now avoid cows’ milk products for ethical or allergic/intolerance holistic and tailored formulations to suit all demands. Thus, reasons but don’t want to miss out on its inherent nutritional the company can support manufacturers who are looking to benefits. By adding natural calcium carbonate to these target the bone health market in multiple ways. Osteoporosis nutraceuticals that promote healthy ageing products, manufacturers can take a contemporary approach to should no longer be thought of as an inevitable part of growing fortification. In addition, compared with synthetically produced old. By focusing on prevention and lifestyle changes, including The importance of healthy ageing. that arose from the same ancestral gene before the species calcium salts, naturally derived calcium sources are not only a physical activity and nutrition, people all over the world can Medical developments and improvements to factors such as diverged – provides a crude indication of how similar different better match for modern consumer demands, but also convince avoid much of its devastating impact. food supply and sanitation have contributed to lengthening of species are, and therefore to some extent how good a model because of their high calcium content. Calcium carbonate is human lifespan, which based on OECD statistics1 has been they might represent. Around 85% of human genes have a globally recognized source of calcium that allows for health References increasing at a rate of close to 2 years per decade in recent orthologs in rats and mice – two very commonly used in vivo claims. In order to be able to make a “high in calcium” claim 1 Hernlund E, Svedbom A, Ivergard M, Compston J, et. al. history. Despite this relatively rapid increase in lifespan, there models – and this rises to above 90% in primates. in the EU, a food item must contain 30% of the recommended Osteoporosis in the European Union: Medical Management, is evidence that healthspan – essentially the number of years C. elegans as an in vivo model. daily allowance (RDA) per serving size. A dosage of 15% Epidemiology and Economic Burden. A report prepared in that an individual remains in relative good health and free from The roundworm Caenorhabditis elegans is an invertebrate allows for a “source of calcium” claim. Because of its high total collaboration with the International Osteoporosis Foundation disease – has not increased at the same rate2. So, although and more distantly related to humans than the previously calcium content (approximately 40%), calcium carbonate can (IOF) and the European Federation of Pharmaceutical Industry we may be living longer, our quality of life in these extra years mentioned vertebrate models, with a genome that contains be incorporated at low concentrations to minimize the cost of Associations (EFPIA). Arch Osteoporos 2013 8:136 is not necessarily very high. orthologs for between 40% and 80% of human genes6,7. C. fortification for manufacturers. 2 Website of the International Osteoporosis Foundation, www. Age is a major risk factor in many diseases; whether that is elegans has many of the features that are desired in a model iofbonehealth.org (accessed: 21th July 2017) certain cancers, cardiovascular disease, neurodegenerative species including: small size, high fecundity, short generation Outlook 3 Chapuy MC, Arlot ME, Duboeuf F, et al. (1992) Vitamin D3 diseases such as Alzheimer’s, or declines in our immune time, translucent bodies, a fully sequenced genome, and Omya has developed a natural calcium carbonate portfolio and calcium to prevent hip fractures in elderly women. N Engl J system (immunosenescence) or strength (sarcopenia). The genetic tractability (see review 8). The worm provides a comprising different brands in order to offer the perfect Med 327:1637. process of ageing is not simply the result of accumulation whole organism model with many physiological similarities to functionality for all types of applications – from food fortification 4 Chapuy MC, Pamphile R, Paris E, et al. (2002) Combined of damage in an individual’s cells over time that leads to humans, such as a digestive system and a nervous system. to nutritional supplementation. Thanks to its role as a global calcium and vitamin D3 supplementation in elderly women: a breakdown in their function. Instead ageing involves a Such features led to it being proposed as a model organism distributor, Omya also possesses a comprehensive portfolio confirmation of reversal of secondary hyperparathyroidism and coordinated programme of changes, including notable by Nobel prize winning scientist Sydney Brenner in the of multipurpose ingredients, such as natural food colors, hip fracture risk. Osteoporos Int 13:257. differences to an individual’s epigenome3,4. For better or for 1970s9. Since then it has been heavily used in biological and worse, how an individual interacts with their environment can biomedical research, including areas such as development Omya at SupplySide West 2017 impact this ageing program. As such, positive changes to and cell death, and oncology, and these efforts have led to two factors such as diet and lifestyle can promote healthy ageing, Nobel prizes. C. elegans was also the first animal to have its At booth M179, Omya will present natural and functionalized calcium carbonates for food, nutraceutical, 10 pharmaceutical and personal care applications. Its distribution company in North America, Lipscomb and help to delay the onset of these negative age-related genome sequenced . Lastly, it is recognized as one of the conditions. two preferred whole organism models that support the 3Rs Chemical, is the technical sales organization that partners with leading specialty ingredients producers for At Sibelius, we believe that Nutraceuticals can make a great initiative in animal research (Refine, Reduce, Replace). these markets. contribution towards healthy ageing, but there is a clear need In the context of healthy ageing, C. elegans provides to demonstrate the clinical benefits that such products can a very good model. A significant amount of research into offer. In part this is due to increasing pressure coming from ageing and longevity has been conducted in the worm11 and regulators, with requirements to provide clinical evidence to the core pathways that regulate ageing are well conserved support any marketing claims. However, there is also a need across almost all species tested; from yeast and worms to develop products with proven benefits to help a growing through to insects and mammals. This makes it much more consumer segment to make informed decisions about the likely that treatments with positive effects on the regulation products that they choose to purchase and use. of cellular health and ageing can be successfully translated In vivo models and managing the risk of demonstrating across from these diverse species to humans. For example clinical benefits. common interventions such as calorie- or dietary-restriction, Well publicised drug-development costs from the or treatments with compounds such as rapamycin, have been pharmaceutical industry – as high as $2.9bn to take a single shown to extend lifespan in essentially all organisms that they drug to market5 – demonstrate that proving clinical benefits is a have been tested in. lengthy, costly, and risky process. Although development costs ChronoscreenTM: supporting the development of novel in the Nutraceutical industry may not be on this scale, effective Nutraceuticals to promote healthy ageing. management of risks is just as crucial to success. At Sibelius we take advantage of C. elegans small size and Just as with the Pharmaceutical industry, clinical trials can short lifespan, together with the conservation of ageing-related make a major contribution to Nutraceutical development costs. pathways between species, to screen potential Nutraceutical It is therefore critical to minimise expensive failures at this ingredients for beneficial effects on ageing in a high throughput stage. Pre-clinical in vitro and in vivo research, are commonly manner (See summary in Figure 1). By taking advantage of used to support the identification and characterisation of the genetic tools available for C. elegans – including the use of potential new treatments. In vivo models in particular play an fluorescent markers such as Green Fluorescent Protein (GFP) important role in allowing the safety, efficacy, pharmacology, – our proprietary ChronoscreenTM technology enables us to and pharmacokinetics of potential new treatments to be track the movements of the translucent worms throughout their assessed in whole living organisms prior to application in lifetime. This way we can measure the lifespan in populations humans. of worms in response to treatment with different Nutraceutical In vivo studies are designed to bridge the gap between ingredients to identify those with positive effects. fundamental research and the clinic, and in line with the Extension of lifespan on ChronoscreenTM indicates that the principles of “fail fast”, they help to manage risk before tested ingredient has had a beneficial effect on the regulation committing to increased spending at later, more expensive of cellular ageing, and therefore has delayed the onset of age- stages of a development pipeline. The successful translation related conditions in the worm. Given the strong conservation of results from in vivo models into application in humans is of the pathways of cellular ageing between species, our dependent on a number of factors; but notably a combination premise is that these ingredients should also have beneficial of the organism that is used as the model, and the underlying effects in humans, with the potential to delay the onset of one causes of the disease being tested (e.g. biochemical or or more age related conditions.